Rules and Stereoelectronic Guidelines for the Anionic Nucleophilic Displacement of Furanoside and Furanose O-Sulfonates

Hale, Karl J.; Hough, L.; Manaviazar, Soraya; Calabrese, Andrew

doi:10.1021/acs.orglett.5b00511

Cited by 16 publications

(15 citation statements)

References 61 publications

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“…For the functionalisation on C2 we first investigated the inversion of the C2‐triflates 29 – 32 , generated from the corresponding C2‐alcohols 25 – 28 with a suitable azide or fluoride nucleophile (Scheme B) . Inversion of the ribosyl C2‐OTf group in 29 by using an excess of NaN 3 in DMF at 80 °C proceeded smoothly to give the 2‐azidoarabinoside 34 in high yield (see Table , entry 1, conditions A).…”

Section: Resultsmentioning

confidence: 99%

“…For the functionalisation on C2 we first investigated the inversion of the C2-triflates 29-32,g eneratedf rom the corre-spondingC 2-alcohols 25-28 [32][33][34][35] with as uitable azide or fluoride nucleophile (Scheme 1B). [36] Inversion of the ribosyl C2-OTf group in 29 by using an excesso fN aN 3 in DMF at 80 8Cp roceeded smoothly to give the 2-azidoarabinoside 34 in high yield (see Ta ble 1, entry 1, conditions A). The inversion of 29 by using tetrabutylammonium fluoridea st he source of the fluoride nucleophile in THF at ambient temperature gave 38 in good yield (71 %, Table 1, entry 2, conditions B).…”

Section: Synthesismentioning

confidence: 99%

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Furanosyl Oxocarbenium Ion Conformational Energy Landscape Maps as a Tool to Study the Glycosylation Stereoselectivity of 2‐Azidofuranoses, 2‐Fluorofuranoses and Methyl Furanosyl Uronates

Vorm

Hansen

Rijssel

et al. 2019

Chemistry A European J

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The 3D shape of glycosyl oxocarbenium ions determines their stability and reactivity and the stereochemical course of S N 1 reactions taking place on these reactive intermediates is dictated by the conformation of these species. The nature and configuration of functional groups on the carbohydrate ring affect the stability of glycosyl oxocarbenium ions and control the overall shape of the cations. We herein map the stereoelectronic substituent effects of the C2‐azide, C2‐fluoride and C4‐carboxylic acid ester on the stability and reactivity of the complete suite of diastereoisomeric furanoses by using a combined computational and experimental approach. Surprisingly, all furanosyl donors studied react in a highly stereoselective manner to provide the 1,2‐ cis products, except for the reactions in the xylose series. The 1,2‐ cis selectivity for the ribo ‐, arabino ‐ and lyxo ‐configured furanosides can be traced back to the lowest‐energy 3 E or E 3 conformers of the intermediate oxocarbenium ions. The lack of selectivity for the xylosyl donors is related to the occurrence of oxocarbenium ions adopting other conformations.

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Section: Resultsmentioning

confidence: 99%

Section: Synthesismentioning

confidence: 99%

Furanosyl Oxocarbenium Ion Conformational Energy Landscape Maps as a Tool to Study the Glycosylation Stereoselectivity of 2‐Azidofuranoses, 2‐Fluorofuranoses and Methyl Furanosyl Uronates

Vorm

Hansen

Rijssel

et al. 2019

Chemistry A European J

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“…The importance of these nucleophilic substitutions is underlined by the review of Hale and Hough (2015). This synthetic problem is of a challenge and merits a careful evaluation of the conditions.…”

Section: Methodsmentioning

confidence: 99%

C-3 epimers of sugar amino acids as foldameric building blocks: improved synthesis, useful derivatives, coupling strategies

et al. 2016

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To obtain key sugar derivatives of making homooligomeric foldamers or α/β-chimera peptides, economic and multigram scale synthetic methods were to be developed. Though described in the literature, the cost-effective making of both 3-amino-3-deoxy-ribofuranuronic acid (H-tX-OH) and its C-3 epimeric stereoisomer, the 3-amino-3-deoxy-xylofuranuronic acid (H-cX-OH) from D-glucose is described here. The present synthetic route elaborated is i) appropriate for large-scale synthesis, ii) reagent costs reduced (e.g. by a factor of 400), iii) yields optimized are ~80% or higher for all six consecutive steps concluding -tX-or -cX-and iv) reaction times shortened. Thus, a new synthetic route step-by-step optimized for yield, cost, time and purification is given both for D-xylo and D-riboamino-furanuronic acids using sustainable chemistry (e.g. less chromatography with organic solvents; using continuous flow reactor). Multigram scale syntheses of these β-sugar amino acids, β-SAAs, now available on a larger scale made possible to test and optimize coupling reactions and conditions of making α/β-chimera peptides. Our study encompasses necessary building blocks (e.g. -X-OMe, -X-O i Pr, -X-NHMe, Fmoc-X-OH) and key coupling reactions making -Aaa-tX-Aaa-or -Aaa-tX-tXAaa-type "inserts". Completed for both stereoisomers of X, including the newly synthetized FmoccX-OH, producing longer oligomers for drug design and discovery is more of a reality than a wish. 2Graphical abstract: From D-glucose in 6 (7) steps both C-3 epimers of an azido-furanuronic acid (cAFU and tAFU) are obtained. Yield optimized, scalable and robust reactions made possible to get β-sugar amino acids in a more environment-friendly way. Useful derivatives were synthesized and probed as key intermediates of foldameric "Lego element" now ready to be built in into α/β-chimera peptides supporting drug design and discovery.3

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“…Competing intramolecular cyclisation reactions between both purine and pyrimidine nucleobases and (especially) the 5′-position of the (deoxy)ribofuranoside are frequently observed during both activation [7] and subsequent displacement reactions [8–9]. This competition confounds the kind of systematic analysis developed recently by Hale and co-workers for sulfonate displacement from furanosides [10] and convoluted optimisations of reaction conditions and nucleoside substrate (e.g., the leaving group [11] or nucleobase protection [12]) are therefore often required.…”

Section: Introductionmentioning

confidence: 99%

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

Eguaogie¹,

Conlon²,

Ravalico³

et al. 2017

Beilstein J. Org. Chem.

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Vibration ball-milling in a zirconia-lined vessel afforded clean and quantitative nucleophilic displacement reactions between 4-methoxybenzylthiolate salts and nucleoside 5′-halides or 5′-tosylates in five to 60 minutes. Under these conditions, commonly-encountered nucleoside cyclisation byproducts (especially of purine nucleosides) were not observed. Liquid-assisted grinding of the same 5'-iodide and 5′-tosylate substrates with potassium selenocyanate in the presence of DMF produced the corresponding 5′-selenocyanates in variable yields over the course of between one and eleven hours thereby avoiding the preparation and use of hygroscopic tetrabutylammonium salts.

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Rules and Stereoelectronic Guidelines for the Anionic Nucleophilic Displacement of Furanoside and Furanose O-Sulfonates

Abstract: Rules for predicting anionic SN2 displacement viability in furanose and furanoside sulfonates are presented.

Cited by 16 publications

References 61 publications

Furanosyl Oxocarbenium Ion Conformational Energy Landscape Maps as a Tool to Study the Glycosylation Stereoselectivity of 2‐Azidofuranoses, 2‐Fluorofuranoses and Methyl Furanosyl Uronates

Furanosyl Oxocarbenium Ion Conformational Energy Landscape Maps as a Tool to Study the Glycosylation Stereoselectivity of 2‐Azidofuranoses, 2‐Fluorofuranoses and Methyl Furanosyl Uronates

C-3 epimers of sugar amino acids as foldameric building blocks: improved synthesis, useful derivatives, coupling strategies

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

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